Prospective Comparison Between Ultra Early NKF Versus Standard Cannulation Alone

Pancreatitis Clinical Trial

Official title:

Prospective Comparison Between Ultra Early NKF Versus Standard Cannulation Alone in a Group of High and Low Risk of Pep, Submitted to Pep Prophylaxis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04492137
• Other study ID #: 32/2020
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2020
• Est. completion date: June 30, 2022

Study information

• Verified date: August 2021
• Source: University of Minho
• Contact: Luís Lopes, MD, PhD, MBA
• Phone: 00351932841974
• Email: luis.m.lopes[@]me.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Compare the ultra early fistulotomy strategy with standard cannulation methods for accessing the bile duct during endoscopic retrograde cholangiopancreatography (ERCP)

Description:

1. Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced procedure which is widely used in the diagnosis and treatment of a variety of benign and malignant pancreatobiliary disorders1,2,3,4,5.

Selective cannulation of the common bile duct (CBD) is the most important and challenging step in a biliary endoscopic retrograde cholangiopancreatography6,7. However, in the first ERCP, even in experienced hands, biliary cannulation may fail in up to 15 % - 35 % of cases when using standard methods alone8. In this subset of patients, additional cannulation techniques are needed to access the CBD in order to continue with the ERCP.

Precut is the most common strategy used by experienced endoscopists, when conventional methods have failed7. Needle knife fistulotomy (NKF) and conventional precut are the two most common variants. Recently published guidelines recommend opting for NKF, as evidence suggests a lower risk of adverse events, especially pancreatitis, when used early in the biliary cannulation algorithm7,9.

Technically NKF is the creation of an artificial fistula between the most protuberant portion of the papilla, which represents the intraduodenal portion of the CBD and the biliary tract by using a diathermic cutter of the needle type6,10,11,12,13,14,15,16,17,18. Its big advantage over conventional precut is that it avoids the contact of the cutting device with the papillary orifice and therefore avoiding direct thermal injury to the pancreatic duct.

Although NKF was originally developed as a rescue technique, to be used after previous failed standard cannulations attempts, it is being increasingly used at an early stage during ERCP. Given its safety and feasibility some authors even advocate, the once unreasonable, primary use without previous standard cannulation attempts10,11,19,20.

2. Financial resources

All participants included in this study will perform ERCP, laboratory tests and other complementary diagnostic tests after a duly justified medical prescription. Therefore there are no additional costs or consumption of hospital resources.

3. Ethical considerations In this study, participants will be included after informed consent. Anonymity and confidentiality will be safeguarded by assigning an individual numeric code. It will also be explained the possibility of withdrawing from the study at any time, with the guarantee of the total elimination of data. All researchers involved in the study will adhere to the Rules of Ethical Conduct and Best Practices in order to comply with the precepts of the Declaration of Helsinki, the Convention on Human Rights and Biomedicine, the guidelines of the Council for International Organizations of Medical Sciences and the Guide to Good Clinical Practice.

4. Statistical analysis

Qualitative variables will be summarized using absolute and relative frequencies, and quantitative variables will be summarized using the mean and standard deviation or the median and interquartile range, depending on their distribution profiles. The normality of the quantitative variables will be assessed using the histogram distribution.

A sample of 334 (167 in each group) patients will provide 80% power to detect a difference of 5% in pancreatitis rates between the two groups based on a chi-square test, assuming a pancreatitis rate of 1% among primary fistulotomy, 6 and a one-tailed alpha of 0.05.

Relations between categorical variables will be assessed using a chi-square test and Fisher´s exact test. Differences between two or more groups of independent non-normally distributed quantitative variables will be evaluated using a Kruskal-Wallis test.

To explain the risk of pancreatitis, a binomial logistic regression model with multiple predictors will be performed.

The null hypothesis will be rejected when the test statistics p-values are less than <0.05. Statistical analysis, sample size calculation and graphics will be performed using Stata software (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, StataCorp LP)

5. Expected results

The results of this study will contribute to a better understanding of what is the best algorithm to follow when performing an ERCP.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 334
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

From June 1, 2020 to June 1, 2022, all individuals referred for ERCP in the Digestive Endoscopy Unit of Santa Luzia Hospital (Unidade Local de Saúde do Alto Minho) will be invited to participate in the study.

Inclusion Criteria:

• ERCP with indication for biliary access

• Naïve papilla

Exclusion Criteria:

• Flat papillas

• Intradiverticular / Diverticular border papillas

• Patients unable to sign or understand the informed consent

• Patients with surgically altered anatomy

• Patients with tumors of the papilla

• Previous sphincterotomy

• Spontaneous papillary fistula

• Papilla not visualized

Related Conditions & MeSH terms

• Pancreatitis

Intervention

Procedure:
• Cannulation technique
Participants in the ultra early NKF group will be submitted to 2 standard cannulation attempts (2 contacts with the papilla) before starting NKF. If any of these 2 attemps is successful, NKF won't take place. If NKF is indeed performed and cannulation is not achieved within 8 minutes, the endoscopist is free to perform techniques other than NKF. On the other hand, participants in the standard cannulation group in which cannulation is not achieved within 8 minutes can cross-over to other advanced cannulation techniques (e.g. NKF). For ethical reasons we choose to exclude flat and intradiverticular/diverticular border papillas. During ERCP all participants will be submitted to PEP prophylaxis with rectal indomethacin. A pancreatic stent will be placed whenever there is cannulation or opacification of the Wirsung duct. For the purposes of the study, a dedicated form (attached) will be created with the various variables to be analyzed

Locations

Country	Name	City	State
Portugal	Santa Luzia Hospital, ULS Alto Minho	Viana do Castelo

Sponsors (2)

Lead Sponsor	Collaborator
University of Minho	Unidade Local de Saúde do Alto Minho

Country where clinical trial is conducted

Portugal, 

References & Publications (20)

Abu-Hamda EM, Baron TH, Simmons DT, Petersen BT. A retrospective comparison of outcomes using three different precut needle knife techniques for biliary cannulation. J Clin Gastroenterol. 2005 Sep;39(8):717-21. — View Citation

Canena J, Coimbra J, Carvalho D, Rodrigues C, Silva M, Costa M, Horta D, Mateus Dias A, Seves I, Ramos G, Ricardo L, Coutinho AP, Romão C, Veiga PM. Endoscopic bilio-duodenal bypass: outcomes of primary and revision efficacy of combined metallic stents in malignant duodenal and biliary obstructions. Dig Dis Sci. 2014 Nov;59(11):2779-89. doi: 10.1007/s10620-014-3199-y. Epub 2014 May 13. — View Citation

Canena J, Liberato M, Coutinho AP, Marques I, Romão C, Veiga PM, Neves BC. Predictive value of cholangioscopy after endoscopic management of early postcholecystectomy bile duct strictures with an increasing number of plastic stents: a prospective study (with videos). Gastrointest Endosc. 2014 Feb;79(2):279-88. doi: 10.1016/j.gie.2013.07.022. Epub 2013 Sep 5. — View Citation

Canena J, Liberato M, Meireles L, Marques I, Romão C, Coutinho AP, Neves BC, Veiga PM. A non-randomized study in consecutive patients with postcholecystectomy refractory biliary leaks who were managed endoscopically with the use of multiple plastic stents or fully covered self-expandable metal stents (with videos). Gastrointest Endosc. 2015 Jul;82(1):70-8. doi: 10.1016/j.gie.2014.11.038. Epub 2015 Mar 11. — View Citation

Canena J, Lopes L, Fernandes J, Alexandrino G, Lourenço L, Libânio D, Horta D, Giestas S, Reis J. Outcomes of Single-Operator Cholangioscopy-Guided Lithotripsy in Patients with Difficult Biliary and Pancreatic Stones. GE Port J Gastroenterol. 2019 Mar;26(2):105-113. doi: 10.1159/000488508. Epub 2018 May 16. — View Citation

Canena J. Once upon a Time a Guideline Was Used for the Evaluation of Suspected Choledocholithiasis: A Fairy Tale or a Nightmare? GE Port J Gastroenterol. 2018 Jan;25(1):6-9. doi: 10.1159/000481688. Epub 2017 Nov 8. — View Citation

Chen DD, Keswani RN. Is Needle Knife Fistulotomy a Shortcut to Preventing Postendoscopic Retrograde Pancreatitis? Am J Gastroenterol. 2020 Apr;115(4):535-536. doi: 10.14309/ajg.0000000000000553. — View Citation

Donnellan F, Zeb F, Courtney G, Aftab AR. Suprapapillary needleknife fistulotomy: a safe and effective method for accessing the biliary system. Surg Endosc. 2010 Aug;24(8):1937-40. doi: 10.1007/s00464-010-0881-9. Epub 2010 Feb 5. — View Citation

Harewood GC, Baron TH. An assessment of the learning curve for precut biliary sphincterotomy. Am J Gastroenterol. 2002 Jul;97(7):1708-12. — View Citation

Horiuchi A, Nakayama Y, Kajiyama M, Tanaka N. Effect of precut sphincterotomy on biliary cannulation based on the characteristics of the major duodenal papilla. Clin Gastroenterol Hepatol. 2007 Sep;5(9):1113-8. Epub 2007 Aug 6. — View Citation

Jang SI, Kim DU, Cho JH, Jeong S, Park JS, Lee DH, Kwon CI, Koh DH, Park SW, Lee TH, Lee HS. Primary Needle-Knife Fistulotomy Versus Conventional Cannulation Method in a High-Risk Cohort of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis. Am J Gastroenterol. 2020 Apr;115(4):616-624. doi: 10.14309/ajg.0000000000000480. — View Citation

Jin YJ, Jeong S, Lee DH. Utility of needle-knife fistulotomy as an initial method of biliary cannulation to prevent post-ERCP pancreatitis in a highly selected at-risk group: a single-arm prospective feasibility study. Gastrointest Endosc. 2016 Nov;84(5):808-813. doi: 10.1016/j.gie.2016.04.011. Epub 2016 Apr 19. — View Citation

Katsinelos P, Gkagkalis S, Chatzimavroudis G, Beltsis A, Terzoudis S, Zavos C, Gatopoulou A, Lazaraki G, Vasiliadis T, Kountouras J. Comparison of three types of precut technique to achieve common bile duct cannulation: a retrospective analysis of 274 cases. Dig Dis Sci. 2012 Dec;57(12):3286-92. doi: 10.1007/s10620-012-2271-8. Epub 2012 Jun 20. — View Citation

Khatibian M, Sotoudehmanesh R, Ali-Asgari A, Movahedi Z, Kolahdoozan S. Needle-knife fistulotomy versus standard method for cannulation of common bile duct: a randomized controlled trial. Arch Iran Med. 2008 Jan;11(1):16-20. — View Citation

Lee TH, Bang BW, Park SH, Jeong S, Lee DH, Kim SJ. Precut fistulotomy for difficult biliary cannulation: is it a risky preference in relation to the experience of an endoscopist? Dig Dis Sci. 2011 Jun;56(6):1896-903. doi: 10.1007/s10620-010-1483-z. Epub 2010 Nov 17. — View Citation

Lopes L, Dinis-Ribeiro M, Rolanda C. Early precut fistulotomy for biliary access: time to change the paradigm of "the later, the better"? Gastrointest Endosc. 2014 Oct;80(4):634-641. doi: 10.1016/j.gie.2014.03.014. Epub 2014 May 6. — View Citation

Lopes L, Dinis-Ribeiro M, Rolanda C. Safety and efficacy of precut needle-knife fistulotomy. Scand J Gastroenterol. 2014 Jun;49(6):759-65. doi: 10.3109/00365521.2014.898085. Epub 2014 Mar 18. — View Citation

Mavrogiannis C, Liatsos C, Romanos A, Petoumenos C, Nakos A, Karvountzis G. Needle-knife fistulotomy versus needle-knife precut papillotomy for the treatment of common bile duct stones. Gastrointest Endosc. 1999 Sep;50(3):334-9. — View Citation

Testoni PA, Mariani A, Aabakken L, Arvanitakis M, Bories E, Costamagna G, Devière J, Dinis-Ribeiro M, Dumonceau JM, Giovannini M, Gyokeres T, Hafner M, Halttunen J, Hassan C, Lopes L, Papanikolaou IS, Tham TC, Tringali A, van Hooft J, Williams EJ. Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2016 Jul;48(7):657-83. doi: 10.1055/s-0042-108641. Epub 2016 Jun 14. — View Citation

Testoni PA, Testoni S, Giussani A. Difficult biliary cannulation during ERCP: how to facilitate biliary access and minimize the risk of post-ERCP pancreatitis. Dig Liver Dis. 2011 Aug;43(8):596-603. doi: 10.1016/j.dld.2011.01.019. Epub 2011 Mar 4. Review. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Comparison of adverse event rate between the two strategies	30 days from the procedure
Primary	Technical success	Comparison of technical success between the two strategies	1 day (same day of the procedure)
Secondary	Adverse event rate among sub groups	Comparison of adverse event rate among sub groups (high and low risk of pancreatitis)	30 days from the procedure
Secondary	Technical success among sub groups	Comparison of technical success rate among sub groups (high and low risk of pancreatitis)	1 day (same day of the procedure)